LY3405105 / Eli Lilly - LARVOL DELTA

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1 | N=54 | Terminated | Sponsor: Eli Lilly and Company | Phase classification: P1a/1b ➔ P1

Phase classification • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors. (PubMed, Oncologist) - P1a/1b | "The MTD of LY3405105 monotherapy was 20 mg QD. The most common toxicities were gastrointestinal adverse events, myelosuppression, fatigue, and asthenia. Limited clinical activity was observed in this phase I trial, and there are no plans for further development."

Journal • Metastases • P1 data • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Oncology • Pain • Solid Tumor • CDK7

Discovery of XNW9015, a potent, selective, and CNS-penetrating covalent inhibitor of CDK7 with excellent in vivo antitumor activities (AACR 2023) - "In the Palbociclib-resistant breast cancer cell line MCF-7, XNW9015 exhibited antiproliferative activity, with an IC50 of 81nM, while neither Palbociclib nor Fulvestrant can inhibit the cell viability...XNW9015 exhibited superior rodent pharmacokinetic characteristics when compared to LY3405105 (Eli Lilly and Company, WO2019099298)...In summary, XNW9015 has demonstrated potent in vitro and in vivo antitumor effects, favorable pharmacokinetic and toxicological properties. XNW9015 has become a potential clinical candidate for cancer therapeutics, both as monotherapies and in combination settings."

Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • CDK1 • CDK12 • CDK2 • CDK7 • CDK9

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=54; Terminated; Sponsor: Eli Lilly and Company; Completed ➔ Terminated; The study was terminated for lack of sufficient efficacy.

Clinical • Trial termination • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=180; Recruiting; Sponsor: Eli Lilly and Company; Trial completion date: May 2022 ➔ Jun 2021; Trial primary completion date: May 2022 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=55; Completed; Sponsor: Eli Lilly and Company; Active, not recruiting ➔ Completed; N=180 ➔ 55; Trial completion date: Jun 2021 ➔ Feb 2021

Clinical • Enrollment change • Trial completion • Trial completion date • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=215; Recruiting; Sponsor: Eli Lilly and Company; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=180; Active, not recruiting; Sponsor: Eli Lilly and Company; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=215; Not yet recruiting; Sponsor: Eli Lilly and Company

Clinical • New P1 trial • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=215; Suspended; Sponsor: Eli Lilly and Company; Recruiting ➔ Suspended

Clinical • Trial suspension • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

A Study of LY3405105 in Participants With Advanced Cancer (clinicaltrials.gov) - P1a/1b; N=215; Recruiting; Sponsor: Eli Lilly and Company; Suspended ➔ Recruiting

Clinical • Enrollment open • Breast Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • ARID1A • KDM6A • KMT2C • KMT2D • MLL2 • SMARCA2 • SMARCB1 • SS18

CDK7 inhibitors as anticancer drugs. (PubMed, Cancer Metastasis Rev) - P1, P1/2, P1a/1b | "Four CDK7i, ICEC0942 (CT7001), SY-1365, SY-5609 and LY3405105, have now progressed to Phase I/II clinical trials. Here we describe the work that has led to the development of selective CDK7i, the current status of the most advanced clinical candidates, and discuss their potential importance as cancer therapeutics, both as monotherapies and in combination settings. ClinicalTrials.gov Identifiers: NCT03363893; NCT03134638; NCT04247126; NCT03770494."

Journal • Review